Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR

CD4(+) T regulatory (T(reg)) cells are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells they regulate. To understand this heterogeneity, we combined single-cell RNAseq, activation reporter and TCR analysis to profile thousands of T(re...

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Autores principales: Zemmour, David, Zilionis, Rapolas, Kiner, Evgeny, Klein, Allon M, Mathis, Diane, Benoist, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069633/
https://www.ncbi.nlm.nih.gov/pubmed/29434354
http://dx.doi.org/10.1038/s41590-018-0051-0
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author Zemmour, David
Zilionis, Rapolas
Kiner, Evgeny
Klein, Allon M
Mathis, Diane
Benoist, Christophe
author_facet Zemmour, David
Zilionis, Rapolas
Kiner, Evgeny
Klein, Allon M
Mathis, Diane
Benoist, Christophe
author_sort Zemmour, David
collection PubMed
description CD4(+) T regulatory (T(reg)) cells are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells they regulate. To understand this heterogeneity, we combined single-cell RNAseq, activation reporter and TCR analysis to profile thousands of T(regs) or T(convs) from mouse lymphoid organs or human blood. T(reg) and T(conv) pools showed areas of overlap, as resting “furtive” T(regs) with overall similarity to T(conv), or as a convergence of activated states. All T(regs) express a small core of FoxP3-dependent transcripts, onto which additional programs are added less uniformly. Among suppressive functions, Il2ra and Ctla4 were quasi-constant, inhibitory cytokines being more sparsely distributed. TCR signal intensity didn’t affect resting/activated T(reg) proportions, but molded activated T(reg) programs. The main lines of T(reg) heterogeneity in mice were strikingly conserved in human blood. These results reveal unexpected TCR-shaped states of activation, providing a framework to synthesize previous observations about T(reg) heterogeneity.
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spelling pubmed-60696332018-08-12 Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR Zemmour, David Zilionis, Rapolas Kiner, Evgeny Klein, Allon M Mathis, Diane Benoist, Christophe Nat Immunol Article CD4(+) T regulatory (T(reg)) cells are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells they regulate. To understand this heterogeneity, we combined single-cell RNAseq, activation reporter and TCR analysis to profile thousands of T(regs) or T(convs) from mouse lymphoid organs or human blood. T(reg) and T(conv) pools showed areas of overlap, as resting “furtive” T(regs) with overall similarity to T(conv), or as a convergence of activated states. All T(regs) express a small core of FoxP3-dependent transcripts, onto which additional programs are added less uniformly. Among suppressive functions, Il2ra and Ctla4 were quasi-constant, inhibitory cytokines being more sparsely distributed. TCR signal intensity didn’t affect resting/activated T(reg) proportions, but molded activated T(reg) programs. The main lines of T(reg) heterogeneity in mice were strikingly conserved in human blood. These results reveal unexpected TCR-shaped states of activation, providing a framework to synthesize previous observations about T(reg) heterogeneity. 2018-02-12 2018-03 /pmc/articles/PMC6069633/ /pubmed/29434354 http://dx.doi.org/10.1038/s41590-018-0051-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zemmour, David
Zilionis, Rapolas
Kiner, Evgeny
Klein, Allon M
Mathis, Diane
Benoist, Christophe
Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title_full Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title_fullStr Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title_full_unstemmed Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title_short Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
title_sort single-cell gene expression reveals a landscape of regulatory t cell phenotypes shaped by the tcr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069633/
https://www.ncbi.nlm.nih.gov/pubmed/29434354
http://dx.doi.org/10.1038/s41590-018-0051-0
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